Receptor binds cell polyamine

A new synthetic receptor binds strongly with spermine, a polyamine that regulates cell proliferation and influences tumor growth and apoptosis (J. Am. Chem. Soc. 2006, 128, 10253). Sijbren Otto and coworkers at Cambridge University used monothiol and dithiol building blocks to build a dynamic combinatorial library of linear and macrocyclic disulfides. The building blocks were equipped with carboxylate groups and tailored to recognize protonated amine groups in spermine (shown, left). The library delivered a cyclic tetramer (shown, right) with sufficient affinity for spermine to remove it from its natural host, DNA, in vitro. In low concentrations, spermine induces the nucleic acid to switch from its normal right-handed double helix to a left-handed one. The Cambridge team showed that when the synthetic receptor sequesters spermine, DNA reverts back to its right-handed conformation. The authors suggest that their receptor may be a promising lead for developing novel therapeutics or molecular probes that may help unravel the poorly understood role of polyamines in cell biology.